Target (protein/gene name): Dihydropteroate synthase 2
E.C Number: 2.5.1.15
NCBI Gene # or RefSeq#: NC_000962.3
PBD ID: 2VP8
Organism: Mycobacterium Tuberculosis
Etiologic Risk Group: N/A
Disease Information: Mycobacterium is an organism that induces the disease Tuberculosis. Mycobacterium does this through the formation of aerosol droplets onto lung-alveolar spaces in the body. The disease was it's first sighting in dirt found on earth but was soon found in animal, specifically cows, which in turn passed on what was called M.bovis (M.tuberculosis) to humans. It was found that over the years the disease has been quite fatal and it wasn't until the 20th century that vaccines and antibiotics were discovered to treat this disease. Although there are discovered treatments for this disease, there is still fatal cases around the world today. The most commons symptoms seen affect the lungs and nervous system.

Links:
1. What is Tuberculosis?
2. Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence


Essentiality:
Dihydropteroate synthase participates in the biosynthetic pathways for folate (in bacteria, plants and fungi) and methanopterin (in archaea). The enzyme exists in varying types of multifunctional proteins in different organisms such as the plant Arabidopsis thaliana and the yeast Saccharomyces cerevisiae.

Link:
Expasy Page


Druggable Target:
A Promising Target for Novel Anti-Malarial Chemotherapy


Assayable Enzyme Target:
http://www.ajtmh.org/docserver/fulltext/14761645/72/2/0720155.pdf?expires=1525621478&id=id&accname=guest&checksum=7B23BE897925EAA8A03DB545CD85E784

A simple method to detect plasmodium falciparum single nucleotide polymorphisms in many proteins including Dihydropteroate synthase using polymerase chain reaction and enzyme linked immunosorbent assay-based technology.

Brenda:
http://www.brenda-enzymes.org/enzyme.php?ecno=2.5.1.15


Structure:
external image 2vp8.pdb1-500.jpg


Pairwise alignment of BlastP:
<span style="background-color: #ffffff; color: #222222; font-size: 11.869px;">Query  1    MNKSLIIFGIVNITSDSFSDGGRYLAPDAAIAQARKLMAEGADVIDLGPASSNPDAAPVS  60
            MNKSLIIFGIVNITSDSFSDGGRYLAPDAAIAQARKLMAEGADVIDLGPASSNPDAAPVS
Sbjct  13   MNKSLIIFGIVNITSDSFSDGGRYLAPDAAIAQARKLMAEGADVIDLGPASSNPDAAPVS  72
 
Query  61   SDTEIARIAPVLDALKADGIPVSLDSYQPATQAYALSRGVAYLNDIRGFPDAAFYPQLAK  120
            SDTEIARIAPVLDALKADGIPVSLDSYQPATQAYALSRGVAYLNDIRGFPDAAFYPQLAK
Sbjct  73   SDTEIARIAPVLDALKADGIPVSLDSYQPATQAYALSRGVAYLNDIRGFPDAAFYPQLAK  132
 
Query  121  SSAKLVVMHSVQDGQADRREAPAGDIMDHIAAFFDARIAALTGAGIKRNRLVLDPGMGFF  180
            SSAKLVVMHSVQDGQADRREAPAGDIMDHIAAFFDARIAALTGAGIKRNRLVLDPGMGFF
Sbjct  133  SSAKLVVMHSVQDGQADRREAPAGDIMDHIAAFFDARIAALTGAGIKRNRLVLDPGMGFF  192
 
Query  181  LGAAPETSLSVLARFDELRLRFDLPVLLSVSRKSFLRALTGRGPGDVGAATLAAELAAAA  240
            LGAAPETSLSVLARFDELRLRFDLPVLLSVSRKSFLRALTGRGPGDVGAATLAAELAAAA
Sbjct  193  LGAAPETSLSVLARFDELRLRFDLPVLLSVSRKSFLRALTGRGPGDVGAATLAAELAAAA  252
 
Query  241  GGADFIRTHEPRPLRDGLAVLAALKETARIR  271
            GGADFIRTHEPRPLRDGLAVLAALKETARIR
Sbjct  253  GGADFIRTHEPRPLRDGLAVLAALKETARIR  283
 
</span>
Query Coverage: 100%
Max % Identities: 100%
% Positives: 100%
Chain used for Homology: A


Similarity to Human: No similarity to human was found

Inhibitors:
In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthase, DHPS. DHPS catalyses the conversion of PABA (para-aminobenzoate) to dihydropteroate, a key step in folate synthesis.

Folate Inhibitors

Expression:
The genes for dihydropteroate synthase of Mycobacterium tuberculosis were expressed under control of the T5 promoter in a dihydropteroate synthase-deficient strain of Escherichia coli. Using three chromatography steps, M. tuberculosis can be purified.

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.577.1166&rep=rep1&type=pdf

Transmembrane Bound Regions:
There are 4 Transmembrane Bound regions

TMpred graph Image
external image download.php?file=TMPRED.15337.5016.gif

TMpred page Link:
https://embnet.vital-it.ch/cgi-bin/TMPRED_form_parser

CDS Gene Sequence:
<span style="background-color: #ffffff; font-family: monospace,serif;">>NC_000962.3:1351191-1352147 Mycobacterium tuberculosis H37Rv, complete genome
GTGCGTTCAACACCGCCGGCCTCAGCCGGTCGTTCAACACCGCCGGCGTTAGCCGGCCATTCAACACCGC
CGGCGTTAGCCGGCCATTCAACGCTGTGCGGCCGTCCAGTCGCAGGTGATCGTGCGCTGATCATGGCGAT
CGTCAACCGCACCCCGGATTCGTTTTACGACAAGGGTGCGACTTTCAGCGACGCGGCTGCCAGAGACGCG
GTCCACCGGGCCGTCGCCGACGGTGCCGACGTCATCGACGTCGGCGGTGTCAAAGCCGGCCCGGGTGAAC
GCGTCGACGTCGACACCGAGATCACGCGGCTGGTGCCGTTCATCGAATGGCTCCGCGGTGCTTACCCGGA
CCAGCTGATCAGTGTCGACACCTGGCGCGCGCAGGTGGCGAAGGCGGCCTGCGCGGCGGGGGCGGACCTG
ATCAACGACACCTGGGGTGGCGTCGACCCGGCCATGCCCGAGGTGGCCGCCGAGTTCGGCGCGGGCCTGG
TGTGTGCGCACACCGGCGGCGCGCTGCCACGCACGCGACCCTTCCGGGTGAGCTACGGTACGACTACCCG
CGGTGTGGTGGATGCTGTGATTAGCCAGGTCACAGCCGCCGCCGAGCGGGCCGTCGCGGCCGGGGTGGCC
CGCGAGAAGGTGTTGATCGACCCGGCACACGACTTCGGCAAGAACACCTTCCATGGGCTGCTGCTATTGC
GACACGTGGCCGATCTTGTTATGACCGGGTGGCCCGTGCTGATGGCTTTGAGCAACAAGGACGTTGTCGG
GGAGACTCTGGGCGTGGATTTGACCGAACGGCTTGAGGGAACGCTGGCAGCCACCGCGTTGGCTGCGGCC
GCCGGGGCGCGCATGTTTCGGGTGCATGAGGTCGCCGCCACCCGGCGGGTGCTGGAAATGGTGGCATCGA
TTCAGGGGGTCCGGCCGCCGACGCGCACGGTGAGAGGACTCGCATGA</span>

Protein Sequence:
<span style="background-color: #ffffff; font-family: monospace,serif;">>NC_000962.3:1351191-1352147 Mycobacterium tuberculosis H37Rv, complete genome
GTGCGTTCAACACCGCCGGCCTCAGCCGGTCGTTCAACACCGCCGGCGTTAGCCGGCCATTCAACACCGC
CGGCGTTAGCCGGCCATTCAACGCTGTGCGGCCGTCCAGTCGCAGGTGATCGTGCGCTGATCATGGCGAT
CGTCAACCGCACCCCGGATTCGTTTTACGACAAGGGTGCGACTTTCAGCGACGCGGCTGCCAGAGACGCG
GTCCACCGGGCCGTCGCCGACGGTGCCGACGTCATCGACGTCGGCGGTGTCAAAGCCGGCCCGGGTGAAC
GCGTCGACGTCGACACCGAGATCACGCGGCTGGTGCCGTTCATCGAATGGCTCCGCGGTGCTTACCCGGA
CCAGCTGATCAGTGTCGACACCTGGCGCGCGCAGGTGGCGAAGGCGGCCTGCGCGGCGGGGGCGGACCTG
ATCAACGACACCTGGGGTGGCGTCGACCCGGCCATGCCCGAGGTGGCCGCCGAGTTCGGCGCGGGCCTGG
TGTGTGCGCACACCGGCGGCGCGCTGCCACGCACGCGACCCTTCCGGGTGAGCTACGGTACGACTACCCG
CGGTGTGGTGGATGCTGTGATTAGCCAGGTCACAGCCGCCGCCGAGCGGGCCGTCGCGGCCGGGGTGGCC
CGCGAGAAGGTGTTGATCGACCCGGCACACGACTTCGGCAAGAACACCTTCCATGGGCTGCTGCTATTGC
GACACGTGGCCGATCTTGTTATGACCGGGTGGCCCGTGCTGATGGCTTTGAGCAACAAGGACGTTGTCGG
GGAGACTCTGGGCGTGGATTTGACCGAACGGCTTGAGGGAACGCTGGCAGCCACCGCGTTGGCTGCGGCC
GCCGGGGCGCGCATGTTTCGGGTGCATGAGGTCGCCGCCACCCGGCGGGTGCTGGAAATGGTGGCATCGA
TTCAGGGGGTCCGGCCGCCGACGCGCACGGTGAGAGGACTCGCATGA
</span>

Do Not Need this info for Spring (but still copy these lines to your Target page for now)
Primer design results for pNIC-Bsa4 cloning (list seqeunces of all of your ~40 nt long primers):
(link to DNA Works output text file - that should be saved in your Google Docs folder after you did the primer design protocol)
-- Ask a mentor, Dr. B, or a fellow researcher -how to link a GDocs file if you are not sure how to.